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AR076251A1 - INHIBITORS OF THE SERINE MACROCICLIC PROTEASE - Google Patents

INHIBITORS OF THE SERINE MACROCICLIC PROTEASE

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Publication number
AR076251A1
AR076251A1 ARP100101201A ARP100101201A AR076251A1 AR 076251 A1 AR076251 A1 AR 076251A1 AR P100101201 A ARP100101201 A AR P100101201A AR P100101201 A ARP100101201 A AR P100101201A AR 076251 A1 AR076251 A1 AR 076251A1
Authority
AR
Argentina
Prior art keywords
heterocyclyl
alkynyl
alkyl
cycloalkyl
heteroaryl
Prior art date
Application number
ARP100101201A
Other languages
Spanish (es)
Original Assignee
Idenix Pharmaceuticals Inc
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Filing date
Publication date
Application filed by Idenix Pharmaceuticals Inc filed Critical Idenix Pharmaceuticals Inc
Publication of AR076251A1 publication Critical patent/AR076251A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/005—Enzyme inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Virology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicinal Preparation (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Compuestos inhibidores de la proteasa serina macrocíclica, composiciones farmacéuticas que comprenden los compuestos y sus procesos de preparacion. También métodos para su uso para el tratamiento de una infeccion de HCV en un huésped que lo necesite. Reivindicacion 1: Un compuesto de formula 1 o 2 o un unico enantiomero, una mezcla racémica, una mezcla de diastereomeros, o su variante isotopica; o su sal, solvato, o prodroga farmacéuticamente aceptable; en donde: R5 es -OH, -NR8R9, -NHS(O)2R8, -NHS(O)2NR8R9, -NHC(O)R8, -NHC(O)NR8R9, -C(O)R8, o -C(O)NR8R9 en donde cada R8 es independientemente hidrogeno, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, cicloalquilo C3-7, arilo C6-14, heteroarilo, heterociclilo, alquil C1-6-cicloalquileno C3-7, -CH2NR8aR8b, -CH(R8c)NR8aR8b, -CHR8cCHR8dNR8aR8b, o -CH2CR8cR8dNR8aR8b, en donde cada R8a, Rc, y R8d es independientemente hidrogeno, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, cicloalquilo C3-7, arilo C6-14, aralquilo C7-15, heteroarilo, o heterociclilo, y cada R8b es independientemente hidrogeno, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, cicloalquilo C3-7, arilo C6-14, aralquilo C7-15, heteroarilo, heterociclilo, -C(O)R11, -C(O)OR11, -C(O)NR11R12, -C(=NR13)NR11 R12, -S(O)R11, -S(O)2R11, -S(O)NR11R12, o -S(O)2NR11R12, en donde cada R11, R12, y R13 es independientemente hidrogeno, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, cicloalquilo C3-7, arilo C6-14, aralquilo C7-15, heteroarilo, o heterociclilo; o R11 y R12 junto con el átomo de N al cual están unidos forman heterociclilo; o R8a y R8b junto con el átomo de N al cual están unidos forman heterociclilo; y cada R9 es independientemente hidrogeno, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, cicloalquilo C3-7, arilo C6-14, aralquilo C7-15, heteroarilo, o heterociclilo, o R8 y R9 junto con el átomo de N al cual están unidos forman heterociclilo; R6 y L son (i) o (ii; (i) R6 es hidrogeno, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, cicloalquilo C3-7, arilo C6-14, heteroarilo, o heterociclilo, y L es un enlace, alquileno C1-6, alquenileno C2-6, alquinileno C2-6, cicloalquileno C3-7, -X-, o -(CR6aR6b)pX-; en donde p es un entero de 1, 2, o 3; R6 y R6b son cada uno independientemente hidrogeno, halo, ciano, hidroxilo, o alcoxi; y X es -C(O)-, -C(O)O-, -C(O)NR14-, -C(=NR14)NR15-, -O-, -OC(O)O-, -OC(O)NR14-, -OC(=NR14)NR15-, -OP(O)(OR14)-, -NR14-, -NR14C(O)NR15-, -NR14C(=NR15)NR16-, -NR14S(O)NR15-, -NR14S(O)2NR15-; -S-, -S(O)-, -S(O)2-, -S(O)NR14-, -S(O)2NR14- o -P(O)(OR14)-, en donde cada R14, R15, y R16 es independientemente hidrogeno, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, cicloalquilo C3-7, arilo C6-14, aralquilo C7-15, heteroarilo, o heterociclilo, o (ii) -L-R6 es -O-N=CR6cR6d, en donde cada R6c y R6d es independientemente hidrogeno, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, cicloalquilo C3-7, arilo C6-14, aralquilo C7-15, heteroarilo, o heterociclilo, o R6c y R6d junto con el átomo de C al cual están unidos forman cicloalquilideno C3-15, arilideno C6-14, heteroarilideno, o heterociclilideno; Q1 es -O-, -N(R17)-, -C(R18R19)-, o -CR17(NR18R19)-; en donde cada R17 y R18 es independientemente hidrogeno, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, cicloalquilo C3-7, arilo C6-14, aralquilo C7-15, heteroarilo, o heterociclilo, y cada R19 es independientemente -R20, -C(O)R20, -C(O)OR20, -C(O)NR21R22, -C(=NR20)NR21R22, -S(O)R20, o -S(O)2R20; donde cada R20, R21, y R22 es independientemente hidrogeno, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, cicloalquilo C3-7, arilo C6-14, aralquilo C7-15, heteroarilo, o heterociclilo, o R21 y R22 junto con el átomo de N al cual están unidos forman heterociclilo; o R18 y R19 junto con el átomo de C o N al cual están unidos forman cicloalquilo C3-7o heterociclilo; Q2 es alquileno C3-9, alquenileno C3-9, o alquinileno C3-9, cada uno conteniendo opcionalmente uno a tres heteroátomos en la cadena, seleccionado independientemente de O, N, y S; U y V son cada uno independientemente N o CH; con la condicion que al menos uno de U o V es N; y m es un entero de 0 o 1; y n es un entero de 1 o 2; con la condicion de que la suma de m mas n es 2 o 3; en donde cada alquilo, alquileno, alquenilo, alquenileno, alquinilo, alquinileno, cicloalquilo, cicloalquileno, arilo, aralquilo, heterociclilo, y heteroarilo está sustituido opcionalmente con uno o más grupos, cada uno seleccionado independientemente de (a) ciano, halo, y nitro; (b) alquilo C1-6, alquenilo C2-6, alquinilo C2-6, cicloalquilo C3-7, arilo C6-14, aralquilo C7-15, heteroarilo, y heterociclilo, cada uno sustituido opcionalmente con uno o más, en una realizacion, uno, dos, tres, o cuatro, sustituyentes Q; y (c) -C(O)Ra, -C(O)ORa, -C(O)NRbRc, -C(NRa)NRbRc, -ORa, -OC(O)Ra, -OC(O)ORa, - OC(O)NRbRc, -OC(=NRa)NRbRc, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRbRc, -OS(O)2NRbRc, NRbRc, -NRaC(O)Rd, -NRaC(O)ORd, -NRaC(O)NRbRc, -NRaC(=NRd)NRbRc, -NRaS(O)Rd, -NRaS(O)2Rd, -NRaS(O)NRbRc, -NRaS(O)2NRbRc, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRbRc, y -S(O)2NRbRc, en donde cada Ra, Rb, Rc, y Rd es independientemente (i) hidrogeno; (ii) alquilo C1-6, alquenilo C2-6, alquinilo C2-6, cicloalquilo C3-7, arilo C6-14, aralquilo C7-15, heteroarilo, o heterociclilo, cada uno sustituido opcionalmente por uno o más, en una realizacion, uno, dos, tres, o cuatro, sustituyentes Q; o (iii) Rb y Rc junto con el átomo de N al cual están unidos forman heterociclilo, opcionalmente sustituido por uno o más, en una realizacion, uno, dos, tres, o cuatro, sustituyentes Q; en donde cada Q se selecciona independientemente del grupo que consiste en (a) ciano, halo, y nitro; (b) alquilo C1-6, alquenilo C2-6, alquinilo C2-6, cicloalquilo C3-7, arilo C6-14, aralquilo C7-15, heteroarilo, y heterociclilo; y (c) -C(O)Re, -C(O)ORe, -C(O)NRfRg, -C(NRe)NRfRg, -ORe, -OC(O)Re, -OC(O)ORe, -OC(O)NRfRg, -OC(=NRe)NRfRg, -OS(O)Re, -OS(O)2Re, -OS(O)NRfRg, -OS(O)2NRfRg, -NRfRg, -NReC(O)Rh, -NReC(O)ORf, -NReC(O)NRfRg, -NReC(=NRh)NRfRg, -NReS(O)Rh, -NReS(O)2Rh, -NReS(O)NRfRg, -NReS(O)2NRfRg, -SRe, -S(O)Re, -S(O)2Re, -S(O)NRfRg, y -S(O)2NRfRg; en donde cada Re, Rf, Rg, y Rh es independientemente (i) hidrogeno; (ii) alquilo C1-6, alquenilo C2-6, alquinilo C2-6, cicloalquilo C3-7, arilo C6-14, aralquilo C7-15, heteroarilo, o heterociclilo, o (iii) Rf y Rg junto con el átomo de N al cual están unidos forman heterociclilo.Macrocyclic serine protease inhibitor compounds, pharmaceutical compositions comprising the compounds and their preparation processes. Also methods for use for the treatment of an HCV infection in a host in need. Claim 1: A compound of formula 1 or 2 or a single enantiomer, a racemic mixture, a mixture of diastereomers, or its isotopic variant; or its pharmaceutically acceptable salt, solvate, or prodrug; where: R5 is -OH, -NR8R9, -NHS (O) 2R8, -NHS (O) 2NR8R9, -NHC (O) R8, -NHC (O) NR8R9, -C (O) R8, or -C ( O) NR8R9 wherein each R8 is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, heteroaryl, heterocyclyl, C 1-6 alkyl-C 3-7 cycloalkylene, -CH2NR8aR8b, -CH (R8c) NR8aR8b, -CHR8cCHR8dNR8aR8b, or -CH2CR8cR8dNR8aR8b, where each R8a, Rc, and R8d is independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C7-6 alkynyl, C7-6 alkynyl, C7-6 alkynyl C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, and each R8b is independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7- aralkyl 15, heteroaryl, heterocyclyl, -C (O) R11, -C (O) OR11, -C (O) NR11R12, -C (= NR13) NR11 R12, -S (O) R11, -S (O) 2R11, -S (O) NR11R12, or -S (O) 2NR11R12, wherein each R11, R12, and R13 is independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6 aryl -14, C7-15 aralkyl, heteroaryl, or het erocyclyl; or R11 and R12 together with the N atom to which they are attached form heterocyclyl; or R8a and R8b together with the N atom to which they are attached form heterocyclyl; and each R9 is independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, or R8 and R9 together with the atom of N to which they are attached form heterocyclyl; R6 and L are (i) or (ii; (i) R6 is hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, heteroaryl, or heterocyclyl, and L it is a bond, C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene, C3-7 cycloalkylene, -X-, or - (CR6aR6b) pX-, wherein p is an integer of 1, 2, or 3; R6 and R6b are each independently hydrogen, halo, cyano, hydroxyl, or alkoxy; and X is -C (O) -, -C (O) O-, -C (O) NR14-, -C (= NR14) NR15-, -O-, -OC (O) O-, -OC (O) NR14-, -OC (= NR14) NR15-, -OP (O) (OR14) -, -NR14-, -NR14C (O ) NR15-, -NR14C (= NR15) NR16-, -NR14S (O) NR15-, -NR14S (O) 2NR15-; -S-, -S (O) -, -S (O) 2-, -S (O) NR14-, -S (O) 2NR14- or -P (O) (OR14) -, wherein each R14, R15, and R16 is independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2 alkynyl- 6, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, or (ii) -L-R6 is -ON = CR6cR6d, wherein each R6c and R6d is independently hydrogen, C1-6 alkyl , C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, aralkyl or C7-15, heteroaryl, or heterocyclyl, or R6c and R6d together with the C atom to which they are attached form C3-15 cycloalkylidene, C6-14 arylidene, heteroarylidene, or heterocyclylidene; Q1 is -O-, -N (R17) -, -C (R18R19) -, or -CR17 (NR18R19) -; wherein each R17 and R18 is independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, and each R19 is independently -R20, -C (O) R20, -C (O) OR20, -C (O) NR21R22, -C (= NR20) NR21R22, -S (O) R20, or -S (O) 2R20; where each R20, R21, and R22 is independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, or R21 and R22 together with the N atom to which they are attached form heterocyclyl; or R18 and R19 together with the C or N atom to which they are attached form C3-7 cycloalkyl heterocyclyl; Q2 is C3-9 alkylene, C3-9 alkenylene, or C3-9 alkynylene, each optionally containing one to three heteroatoms in the chain, independently selected from O, N, and S; U and V are each independently N or CH; with the condition that at least one of U or V is N; and m is an integer of 0 or 1; and n is an integer of 1 or 2; with the proviso that the sum of m plus n is 2 or 3; wherein each alkyl, alkylene, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloalkylene, aryl, aralkyl, heterocyclyl, and heteroaryl optionally is substituted with one or more groups, each independently selected from (a) cyano, halo, and nitro ; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, and heterocyclyl, each optionally substituted with one or more, in one embodiment , one, two, three, or four, substituents Q; and (c) -C (O) Ra, -C (O) ORa, -C (O) NRbRc, -C (NRa) NRbRc, -ORa, -OC (O) Ra, -OC (O) ORa, - OC (O) NRbRc, -OC (= NRa) NRbRc, -OS (O) Ra, -OS (O) 2Ra, -OS (O) NRbRc, -OS (O) 2NRbRc, NRbRc, -NRaC (O) Rd , -NRaC (O) ORd, -NRaC (O) NRbRc, -NRaC (= NRd) NRbRc, -NRaS (O) Rd, -NRaS (O) 2Rd, -NRaS (O) NRbRc, -NRaS (O) 2NRbRc , -SRa, -S (O) Ra, -S (O) 2Ra, -S (O) NRbRc, and -S (O) 2NRbRc, where each Ra, Rb, Rc, and Rd is independently (i) hydrogen ; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, each optionally substituted by one or more, in one embodiment , one, two, three, or four, substituents Q; or (iii) Rb and Rc together with the N atom to which they are attached form heterocyclyl, optionally substituted by one or more, in one embodiment, one, two, three, or four, substituents Q; wherein each Q is independently selected from the group consisting of (a) cyano, halo, and nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, and heterocyclyl; and (c) -C (O) Re, -C (O) ORe, -C (O) NRfRg, -C (NRe) NRfRg, -ORe, -OC (O) Re, -OC (O) ORe, - OC (O) NRfRg, -OC (= NRe) NRfRg, -OS (O) Re, -OS (O) 2Re, -OS (O) NRfRg, -OS (O) 2NRfRg, -NRfRg, -NReC (O) Rh, -NReC (O) ORf, -NReC (O) NRfRg, -NReC (= NRh) NRfRg, -NReS (O) Rh, -NReS (O) 2Rh, -NReS (O) NRfRg, -NReS (O) 2NRfRg, -SRe, -S (O) Re, -S (O) 2Re, -S (O) NRfRg, and -S (O) 2NRfRg; wherein each Re, Rf, Rg, and Rh is independently (i) hydrogen; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, or (iii) Rf and Rg together with the atom of N to which they are attached form heterocyclyl.

ARP100101201A 2009-04-08 2010-04-08 INHIBITORS OF THE SERINE MACROCICLIC PROTEASE AR076251A1 (en)

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EP (1) EP2417134B1 (en)
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AR (1) AR076251A1 (en)
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